Physical Characterization and Safety Evaluation of Folic Acid-conjugated Mesoporous Silica Nanoparticles Loaded with Rhodojaponin III

Background: Rhodojaponin III (RJ-III), a characteristic diterpene of Rhododendron molle G. Don, has a wide range of pharmacological activities including anti-inflammatory, antihypertensive, and analgesic effects. However, further research and development have been limited because of its intense acute toxicity and poor pharmacokinetic profile. Objective: In this study, we propose the construction of folic acid–conjugated mesoporous silica nanoparticles (FA-MSNs) as carriers to deliver RJ-III in an attempt to reduce acute toxicity and improve biomedical applications by prolonging drug release and targeting delivery. Methods: FA-MSNs were synthesized and characterized. RJ-III was then loaded into FA-MSNs (RJIII@ FA-MSNs), and the in vitro drug release profile was assessed. Subsequently, the RJ-III@FAMSNs’ cytotoxicity and targeting efficiency were explored in lipopolysaccharide-activated RAW 264.7 cells, and their acute toxicity was investigated in mice. Results: Spherical FA-MSNs were approximately 122 nm in size. Importantly, the RJ-III@FA-MSNs showed prolonged RJ-III release in vitro. Moreover, in lipopolysaccharide-activated RAW 264.7 cells, RJ-III@FA-MSNs not only reduced the cytotoxicity of RJ-III (P < 0.01), but also showed a good targeting effect from the results of cellular uptake. Additionally, the acute toxicity results demonstrated that RJ-III@FA-MSNs improved the LD50 value of RJ-III in mice by intraperitoneal injection 10-fold. Conclusion: This is the first study to use FA-MSNs as carriers of RJ-III to reduce the acute toxicity of RJ-III. The results confirm the potential for targeted delivery of RJ-III in inflammatory cells to enhance efficacy, as well as providing data for future investigations on anti-inflammatory activity.